Device and method for treating vulnerable plaque

ABSTRACT

A device and method is provided for localized agent delivery through a coronary vessel. In one configuration, the device includes an elongated member having a first and second end with a tip and an aperture positioned near the second end. An injection lumen places the first end of the elongated member in fluid communication with the aperture, permitting fluids such as contrast agent or therapeutic agents to be delivered therebetween. In an exemplary method, the device is tracked through a bend in the coronary anatomy, forcing the tip of the device toward the greater curve and through the vessel wall. The aperture may advanced to the desired location and agents may be delivered through the device into target tissue or space. Other configurations and embodiments of the device and method are presented,

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Ser. No. 60/992,983,filed on Dec. 6, 2007 entitled DEVICE AND METHOD FOR TREATING VULNERABLEPLAQUE, the entirety of which is hereby incorporated by reference.

BACKGROUND OF THE DISCLOSURE

1. The Field of the Invention

This invention, in one configuration, relates generally to the treatmentof coronary disease, and more particularly, to the localized delivery ofbeneficial agents. In one configuration, the invention may be used forthe treatment of vulnerable plaque.

2. The Relevant Technology

Coronary heart disease is generally thought to be caused by thenarrowing of coronary arteries by atherosclerosis, the buildup of fattydeposits in the lining of the arteries. The process that may lead toatherosclerosis begins with the accumulation of excess fats andcholesterol in the blood. These substances infiltrate the lining ofarteries, gradually increasing in size to form deposits commonlyreferred to as plaque or atherosclerotic occlusions. Plaques may narrowthe arterial lumen and impede blood flow. Blood cells may collect aroundthe plaque, eventually creating a blood clot that may block the arterycompletely.

The phenomenon of “vulnerable plaque” has created new challenges inrecent years for the treatment of heart disease. Unlike occlusiveplaques that impede blood flow, vulnerable plaque develops within thearterial walls, but it often does so without substantially narrowing thearterial lumen. Therefore, early symptoms of disease may not be present.As such, conventional methods for detecting heart disease, such as anangiogram, may not detect vulnerable plaque growth in the arterial wall.After death, an autopsy may reveal the plaque congested in arterialwalls that could not have been seen otherwise with currently availablemedical technology.

The intrinsic histological features that may characterize a vulnerableplaque may include increased lipid content, increased macrophage, foamcell and T lymphocyte content, and reduced collagen and smooth musclecell (SMC) content. This fibroatheroma type of vulnerable plaque isoften referred to as “soft”, having a large lipid pool of lipoproteinssurrounded by a fibrous cap. The fibrous cap contains mostly collagen,whose reduced concentration combined with macrophage derived enzymedegradations can cause the fibrous cap of these lesions to rupture underunpredictable circumstances. When ruptured, the lipid core contents,thought to include tissue factor, contact the arterial bloodstream,causing a blood clot to form that can completely block the arteryresulting in an acute coronary syndrome (ACS) event. This type ofatherosclerosis is coined “vulnerable” because of the unpredictabletendency of the plaque to rupture. It is thought that hemodynamic andcardiac forces, which yield circumferential stress, shear stress, andflexion stress, may cause disruption of a fibroatheroma type ofvulnerable plaque. These forces may rise as the result of simplemovements, such as getting out of bed in the morning, in addition to invivo forces related to blood flow and the beating of the heart. It isthought that plaque vulnerability in fibroatheroma types is determinedprimarily by factors which may include: (1) size and consistency of thelipid core; (2) thickness of the fibrous cap covering the lipid core;and (3) inflammation and repair within the fibrous cap.

FIG. 1A illustrates a partial cross section of an artery having anarrowed arterial lumen caused by the presence of occlusiveatherosclerosis. Plaque may accumulate to impede and reduce blood flowthrough the arterial lumen and thus may often cause symptoms (e.g.,angina pectoris). The arrows indicate the direction of blood flowthrough the arterial lumen. FIG. 1B illustrates an occlusiveatherosclerosis within an arterial lumen resulting in significantreduction in lumen patency. This type of atherosclerosis can easily bedetected through current diagnostic methods such as an angiogram. FIG.1B also illustrates, downstream from the occlusive atherosclerosis, afibroatheroma type of vulnerable plaque. The vulnerable plaque, with alipid core, develops mostly within the arterial wall with minimalocclusive effects such that it is not easily detected by currentdiagnostic methods. This is partially due to a phenomenon known as“positive remodeling”, which allows the vessel to respond to thepresence of disease. The fibroatheroma vulnerable plaque has grown intothe positively remodeled arterial wall so that vessel occlusion has notbeen manifested. A fibrous cap surrounds the vulnerable plaque.

FIGS. 2A-2C illustrate a cross-sectional view of the accumulation ofvulnerable plaque in the arterial wall. FIG. 2A illustrates an arterialwall that is not affected by atherosclerosis. The normal arterial wallconsists of an intima layer, a media layer, and an adventitia layer. Theintima is in direct contact with the blood flow within the arteriallumen. The intima consists mainly of a monolayer of endothelial cells.The media consists mostly of smooth muscle cells and extracellularmatrix proteins. The outermost layer of the arterial wall, theadventitia, is primarily collagenous and contains nerves, blood vessels,and lymph vessels. FIG. 2B illustrates the large presence of afibroatheroma type vulnerable plaque surrounded by a fibrous cap withinthe arterial wall. The vulnerable plaque consists mainly of a largelipid core. The fibrous cap layer shields the lumen of the artery fromthe thrombogenic components in the core. FIG. 2C illustrates anocclusive thrombosis event resulting from the rupturing of the fibrouscap. Thrombogenic components in the vulnerable plaque contact luminalblood and cause the thrombotic event.

Autopsy studies and other evidence strongly suggest that the presence ofa current acute coronary syndrome (ACS) event and/or existing thrombusat certain plaque sites may correlate to predicting a future ACS eventin a given patient. The latter indicates the likelihood of a priorthrombotic event (e.g., fibroatheroma rupture) after which the plaquewas able to heal itself, or complete occlusion of the vessel was somehowprevented. Autopsy studies also indicate that it is reasonable to expectthat at least one vulnerable plaque could exist in the majority ofcatheterization laboratory patients being treated for arterial blockagefrom visible occlusive atherosclerosis. Many of the patients at highestrisk, therefore, for future ACS events may already be receivinginterventional treatment, even though current methods to diagnoseocclusive plaques (i.e., non-vulnerable type plaque) may not beeffective for enabling therapy for vulnerable plaque. Furthermore,treating both the occlusive plaques and the vulnerable plaque in oneprocedure might be beneficial and desirable compared to separatetreatments. This would provide a greater convenience to the patient andfor the physician.

One method for the treatment or prevention of disease that has beensuggested is the extravascular administration of anti-microtubule agentssuch as paclitaxel. This method has specifically focused on theadministration of the agents either through the chest wall or externalsurface of the pericardial sac, such as in open chest procedures. Thepericardial sac is the anatomical space between the two layers of thepericardium. Additionally, it has been suggested that the pericardialsac can be accessed through the atrial or ventricular walls of the heartusing catheter guided needles. The procedures described have a majordisadvantage in light of the previous discussion since they do notreadily lend themselves to treating occlusive plaques and vulnerableplaque disease in the same procedure. Additionally, the techniques usedto administer the agents may be significantly different from commoninterventional cardiology techniques such as PTCA, therefore requiringsignificant physician training. Finally, the techniques may be timeconsuming, making them less desirable options for treating coronarydisease.

Another method of treating coronary disease through the delivery of atherapeutic substance includes the use of a catheter-based deviceincorporating a needle whereby the substance can be delivered to thetreatment site, such as a vessel wall or lesion therein. While thisdisclosure may be more similar to conventional interventional techniquesthan the method previously discussed, it may have the disadvantage ofonly providing localized delivery of the substance within the heart. Inthe case of vulnerable plaque, the disease may be profuse and difficultto identify throughout the entire coronary vascular tree. Therefore, thelocalized nature of this method may result in a higher potential ofineffective treatment.

BRIEF SUMMARY OF THE DISCLOSURE

Configurations of the disclosed inventions can be aimed at providing amedical device that can access an extravascular space through the wallof a coronary vessel. The device may subsequently administer atherapeutic agent to treat and/or prevent coronary diseases such asvulnerable plaque. Configurations of the disclosed inventions mayeffectively deliver therapeutic agents to an extravascular space, suchas the pericardial space. Additionally, the treatment may provide for asystemic type of treatment that may improve the chance of effectivelytreating difficult to identify vulnerable plaques.

To achieve at least one of these purposes and/or advantages, and inaccordance with the present disclosure, a medical device is provided forlocalized agent delivery through the wall of a coronary vessel. In aconfiguration, an elongated member is provided having a proximal anddistal end. An access tip can be disposed on the elongated member nearthe distal end. The elongated member may include an internal lumen thatplaces the proximal and distal end of the elongated member in fluidcommunication. In one configuration, the access tip is configured topermit access to the extravascular space by penetrating the coronaryvessel wall, for example. In further accordance with the exemplaryconfiguration, an aperture may be disposed adjacent to the access tipbeing in fluid communication with the internal lumen of the elongatedmember, thereby permitting the delivery of a therapeutic agent throughthe internal lumen into the extravascular space.

In an alternative configuration, the access tip may have a variety ofconfigurations that are suitable for localized agent delivery through acoronary vessel wall. For example, the access tip may have across-sectional profile that is circular or non-circular, and/or may betapered or comprise edges to help penetrate and spread the coronaryvessel wall, thereby easing passage of the elongated member.

In still another alternative configuration, the medical device mayinclude a sealing element, such as a sleeve configured and dimensionedto mate with the medical device surface, the element being moveablebetween a first and second position, whereby the aperture is sealed whenthe sleeve is in one position, but not when the sleeve is in the otherposition.

In an alternative configuration, a medical device is provided thatfurther includes an injection member disposed within the internal lumenof the elongated member. The injection member includes a proximal anddistal end with an injection lumen therebetween. The injection lumenpermits the delivery of a therapeutic agent through the injectionmember. The injection member can be moved between a first position, inwhich the distal end is disposed within the internal lumen of theelongated member, and a second position, in which the distal end ispassed through the aperture of the elongated member.

In a further aspect of the alternative configuration, the medical devicemay further include a biasing member disposed on the elongated membernear the aperture. The biasing member may be an arcuate band, forexample. The biasing member may urge the elongated member toward anon-linear configuration, causing the elongated member to rotationallyorient in a specific manner when passed through a curved path, such asthrough a coronary vessel bend. The natural orientation of the elongatedmember can place the aperture near the outer curve of the bend, therebyensuring that the injection member is directed toward the extravascularspace when it is moved from the first position to the second position.

In yet another alternative configuration, the medical device may furtherinclude multiple apertures disposed adjacent to each other within theelongated member. The apertures may result in a decrease incross-sectional area of the elongated member, increasing the localizedflexibility of the elongated member. By doing so, the elongated membermay tend toward a rotational orientation that may bias one of theapertures toward the outer curve when it is tracked through a coronaryvessel bend. This can also result in an increase in the area of at leastone aperture, since the aperture will be located in a section of theelongated member that is under tension from bending, thereby easing thepassage of the injection member when it is moved from the first positionto the second position.

In yet another configuration, an actuation cord may be associated withthe second end of the elongated member, such that when in a relaxedposition, the elongated member is configured in a natural position, butwhen a tensile load is applied to the actuation cord, the elongatedmember is urged toward a non-linear configuration over a portion of itslength. This non-linear configuration may bias the rotationalorientation of the elongated member and can be used to ease thedirection of the injection member toward the extravascular space, asdescribed above.

In an alternative configuration in accordance with the presentdisclosure, a medical device for localized agent delivery is providedthat includes multiple injection members having injection lumens fordelivering fluids such as contrast solution or therapeutic agentstherethrough. The injection members are disposed within the internallumens of an elongated member, and are moveable from a first position toa second position. The injection members may have a pre-set curved shapethat allows them to follow a curvilinear path as they pass from oneposition to the other. For example, the exposed injection members maycurve outwardly in a substantially longitudinal direction.Alternatively, the injection members may follow a curved path outward ina substantially transverse direction.

In yet another alternative configuration, a medical device for localizedagent delivery is provided that includes an elongated member having afirst and second end placed in fluid communication by an internal lumendisposed therebetween. The medical device may further include adetachable access tip initially placed in communication with theinternal lumen. The detachable tip may be configured to ease insertionthrough the coronary vessel wall and/or to resist retraction into thecoronary vessel after insertion. As a result, retraction of theelongated lumen after insertion of the detachable tip through thecoronary vessel wall may create a dislodging force that may disassociatethe detachable tip from the elongated member.

In a further aspect of the configuration, the detachable access tipfurther includes a therapeutic substance for delivery into theextravascular space. It is further contemplated that the detachable tipmay be formed from a bioabsorbable material.

In another configuration, a device for delivering a therapeutic agentinto the extravascular space through a coronary vessel wall is provided.The device includes an elongated member having a first and second endwith an internal lumen disposed therebetween. The device may include anexpandable structure such as a balloon component disposed near thesecond end of the elongated member. The device may include an apertureadjacent the surface of the expandable structure, the aperture being influid communication with the first end of the elongated member. Thedevice may allow a therapeutic agent to be delivered through theelongated member and/or to exit through the aperture at a sufficientvelocity to cross through the coronary vessel wall into theextravascular space.

In yet another configuration, a stent device is provided that includes aseries of strut elements arranged in an expandable structure. The strutelements may include at least one protrusion directed substantially inthe radial direction. The stent can be expanded from a first low profileconfiguration toward a second high profile configuration by, forexample, placing the stent on a balloon component of a balloon catheterprior to inflating the balloon and expanding the stent. When the stentstructure is expanded, the protrusions may pass through the coronaryvessel wall into the extravascular space. The protrusions may include atherapeutic agent, whereby when the protrusions enter the extravascularspace, the therapeutic agent may be delivered.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and are intended toprovide further explanation of the disclosure claimed. The accompanyingdrawings, which are incorporated in and constitute part of thisspecification, are included to illustrate and provide a furtherunderstanding of the disclosure. Together with the description, thedrawings serve to explain principles of the disclosure.

These and other objects and features of the present disclosure willbecome more fully apparent from the following description and appendedclaims, or may be learned by the practice of the disclosure as set forthhereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

To further clarify the above and other advantages and features of thepresent disclosure, a more particular description of the disclosure willbe rendered by reference to specific configurations or embodimentsthereof which are illustrated in the appended drawings. It isappreciated that these drawings depict only typical configurations orembodiments of the disclosure and are therefore not to be consideredlimiting of its scope. The disclosure will be described and explainedwith additional specificity and detail through the use of theaccompanying drawings in which:

FIG. 1A shows a partial cross-section of an arterial lumen havingocclusive atherosclerosis;

FIG. 1B shows a partial cross-section of an arterial lumen havingocclusive atherosclerosis and vulnerable plaque;

FIGS. 2A-2C show the vessel morphology and the rupturing of a vulnerableplaque;

FIG. 3 illustrates the anatomy of the heart and pericardial sac;

FIG. 4 illustrates a magnified view of a portion of the heart;

FIG. 5 is a side elevation view of one configuration of a device inaccordance with this disclosure;

FIG. 6 is a perspective view of a distal portion of one configuration ofa device in accordance with this disclosure;

FIG. 7 is a perspective view of a distal portion of a furtherconfiguration of a device in accordance with this disclosure;

FIG. 7A is a cross-sectional view of an access tip of a furtherconfiguration of a device in accordance with this disclosure, takenabout line A-A of FIG. 7.

FIG. 8 is a side elevation view of a distal portion of a furtherconfiguration of a device in accordance with this disclosure, wherein asealing component covers an exit port;

FIG. 9 is a side elevation view of a distal end of a furtherconfiguration of a device in accordance with this disclosure, wherein asealing component does not cover an exit port;

FIG. 10 is a side elevation view of a distal end of a furtherconfiguration of a device in accordance with this disclosure having abiasing element in association with the device tip;

FIG. 11 is a perspective view illustrating a distal portion of a furtherconfiguration of a device in accordance with this disclosure disposedwithin a coronary vessel;

FIG. 12 is a perspective view of a distal end of a further configurationof a device in accordance with this disclosure, wherein the device hasmultiple exit ports;

FIG. 13 is a side elevation view of a second end of a furtherconfiguration of a device in accordance with this disclosure, wherein anactuation cord is in a forward position;

FIG. 14 is a side elevation view of a second end of a furtherconfiguration of a device in accordance with this disclosure, wherein anactuation cord is in tension;

FIG. 15 is a side elevation view of a distal portion of a furtherconfiguration of a device in accordance with this disclosure;

FIG. 16 is a side elevation view of a distal end of a furtherconfiguration of a device in accordance with this disclosure;

FIG. 17 is a side elevation view of a distal portion of a furtherconfiguration of a device in accordance with this disclosure, wherein aninjection member is moveable in a substantially longitudinal direction;

FIG. 18 is a side elevation view of a distal portion of a furtherconfiguration of a device in accordance with this disclosure, wherein aninjection member is moveable in a substantially transverse direction;

FIG. 19 is a cross sectional view illustrating a further configurationof a device in accordance with this disclosure, wherein an injectionmember is moveable in a substantially transverse direction, taken aboutline A-A of FIG. 18;

FIG. 20 is a side elevation view of a further configuration of a devicein accordance with this disclosure illustrating an expandable structurein a low profile position;

FIG. 21 is a side elevation view of a further configuration of a devicein accordance with this disclosure illustrating an expandable structurein a high profile position;

FIG. 22 is a side elevation view of a further configuration of anexpandable section that can be incorporated within a device inaccordance with this disclosure;

FIG. 23 is a side elevation view illustrating a system for delivering atherapeutic agent into the extravascular space through a device inaccordance with this disclosure;

FIG. 24 is a side elevation view of a further configuration of a devicein accordance with this disclosure having a detachable access tip;

FIG. 25 is a perspective view of a further configuration of a device inaccordance with this disclosure having a detachable access tip anddisposed within a coronary vessel;

FIG. 26 is a side elevation view of a further configuration of a devicein accordance with this disclosure having a fluid injection lumen;

FIG. 27 is a cross-sectional view of a working region of a device inaccordance with this disclosure having a fluid injection lumen, takenabout line A-A of FIG. 26.

FIG. 28 is a perspective view of a further configuration of a device inaccordance with this disclosure having a fluid injection lumen beingdisposed within a coronary vessel;

FIG. 29 is a side elevation view illustrating a stent device havingprotrusions in accordance with this disclosure;

FIG. 30 is a side elevation view illustrating a further configuration ofa stent device having protrusions in accordance with this disclosure;

FIG. 31 is a cross-sectional view illustrating a further configurationof a stent device having protrusions in accordance with this disclosure,taken about line A-A of FIG. 30.

DETAILED DESCRIPTION

While the present disclosure will be described in detail with referenceto a few specific configurations, the description is illustrative and isnot to be construed as limiting the disclosure. Various modificationscan be made to the illustrated configurations without departing from thespirit and scope of the invention as defined by the appended claims. Itwill be noted here that for a better understanding, like components havebeen designated by like reference numerals through the variousaccompanying figures.

Referring to FIG. 3, the coronary anatomy is shown to illustrate theexemplary anatomical structures associated with the inventiondescription. The heart 10 is identified with related coronary arteries18 disposed substantially on the outer surface of the heart 10.Surrounding the heart 10 is the pericardial sac 14. One function of thepericardial sac 14 is to provide a protective barrier around the heart10 that prevents against infections. The pericardial sac 14 attaches tothe aortic and pulmonary arteries in a superior location relative to theheart 10, shown as attachment location 15 in FIG. 1. It will beunderstood from viewing the anatomical illustration that the pericardialsac 14 and heart 10 define a extravascular space 16. This extravascularspace 16 is normally filled with a fluid. Among other functions, thefluid acts as a lubricant between the heart 10 and the pericardial sac14 as the heart 10 expands, contracts, and moves during normaloperation. The heart 10 therefore provides a natural mixing actionwithin the pericardial space 16. As a result, a fluid that is introducedlocally within the pericardial space 16 will have a tendency to disperseevenly throughout the entire space.

Referring now to FIG. 4, a portion of the outer heart surface is shownto further illustrate the anatomical structures that are relevant tothis invention. The heart 10 is shown, and in this illustration, theright coronary artery 18 has been identified. The right coronary artery18 is a coronary vessel defined by a coronary vessel wall 22. The rightcoronary artery 18 was chosen for this illustration because it normallyincludes a relatively sharp bend as it descends from the aorta andcurves along the surface of the heart 10. When a catheter device istracked through the coronary vessels in an antegrade direction, it has atendency to follow tangential direction line 19, as shown in the figure.The device will cross through the coronary vessel wall 22 into theextravascular space 16 at an access site 20, unless there is sufficientresistance provided by the coronary vessel to retain the device anddirect it along the curve of the vessel instead.

Referring now to FIG. 5, a device for locally delivering a beneficial ortherapeutic agent (it shall be understood that these terms will be usedinterchangeably herein and have the same or similar meanings) is shownthat may be used for accessing the extravascular space 16 of thecoronary anatomy. The agent delivery device 30 includes an elongatedmember 31 with a proximal end 33 and a distal end 35. The elongatedmember 31 is generally configured and dimensioned to be capable oftracking through the cardiovascular system. Further still, the elongatedmember 31 includes an injection lumen formed therein (not shown) thatplaces the proximal end 33 and the distal end 35 in fluid communication.

In one configuration, the elongated member 31 can be constructed from aflexible polymer tubing. Suitable polymers for this purpose includethose typically used in catheter construction. For example, the polymertubing may be formed from nylon, urethane, polyurethane,polyvinylchloride, polyester, PEEK, PTFE, PVDF, Kyner, polyimide, orpolyethylene of various suitable densities. The elongated member 31 maybe further supported by a coiled or braided wire structure over at leasta portion of its length.

In further accordance with the presently described configuration, a luerfitting 34 can be associated with the proximal end 33 of the elongatedmember 31. The luer fitting 34 enables the attachment of an accessorydevice such as a syringe 77 (FIG. 23) or a fluid manifold to the agentdelivery device 30, whereby agents and materials such as therapeuticagents or contrast agents can be delivered through the luer 34 andinjection lumen 36 to the distal end 35.

Therapeutic agents useful in accordance with this disclosure may includea therapeutically effective amount of zotarolimus or derivatives, salts,prodrugs, or esters thereof. In further accordance with the presentdisclosure, the drugs or beneficial agents that can be delivered intothe vessel wall include anti-proliferative and cytostatic drugs such asEverolimus, ABT-578, tacrolimus and pimecrolimus, angiopeptin, calciumchannel blockers such as nifedipine, amlodipine, cilnidipine,lercanidipine, benidipine, trifluperazine, diltiazem and verapamil,fibroblast growth factor antagonists, fish oil (omega 3-fatty acid),histamine antagonists, lovastatin. In addition, topoisomerase inhibitorssuch as etoposide and topotecan, as well as antiestrogens such astamoxifen can be used. Other beneficial agents that are useful inaccordance with this disclosure include anti-inflammatory,antineoplastic, antiplatelet, anti-coagulant, anti-fibrin,antithrombotic, antimitotic, antibiotic, antiallergic and antioxidantcompounds. It will be appreciated that still other types of drugs orbeneficial agents may be delivered and taken up by a vessel wall byusing the devices and methods described herein.

A method for delivering a substance into the extravascular space isprovided in accordance with the present disclosure. The method mayinclude several acts or steps performed in various orders, including theintroduction of a device such as the one described above into thevascular system of a patient. For the purposes of understanding, itshould be realized that the catheter might be tracked into a coronaryvessel, including vessels that are arteries or veins. Although thedevice may access the extravascular space through the vessel wall atvarious locations, in one embodiment, the device accesses theextravascular space through a distal region of the coronary vessel.Achieving access in a distal anatomy may ensure that the distal end 35of the device is within a region of the coronary vessel with relativelylow flow velocities and may reduce the risk of significant blood loss inthe inadvertent event of a vessel dissection. The access tip 32 may beadvanced until it contacts and penetrates the vessel wall. This willhappen, for example, when the device is tracked through a vessel of agiven curvature.

After penetrating the coronary vessel, the device may be advanced farenough to ensure that the access tip 32 of the device is within theextravascular space. A therapeutic agent may then be injected throughthe injection lumen 36 of the device, into the extravascular space. Thesubstance may disperse within the extravascular space by the naturalmixing action of the heart 10 and the substance may be administered tothe desired area(s) through this dispersion.

After delivering the substance, the device may be removed into thecoronary vessel through the access site. Secondary acts or steps may beutilized to close the access site, if blood loss through the access siteappears to be excessive as viewed under medical visualizationtechnologies such as fluoroscopy. An example of a secondary act or stepis the inflation of an angioplasty balloon within the access region tofacilitate closure of the access site.

Referring now to FIG. 6, a distal end 35 of the agent delivery device inaccordance with the present disclosure is shown. An access tip 32 isshown associated with the distal end 35 of the elongated member 31.Aperture 38 is shown located adjacent to distal end 35 of the elongatedmember 31. The aperture 38 can be placed in fluid communication with theproximal end 33 of the elongated member 31 by the injection lumen 36.

According to the present configuration, the access tip 32 is configuredsuch that the cross-sectional area of the access tip 32 adjacent to thedistal end 35 of the elongated member 31 is less than thecross-sectional area near the opposite end of the access tip 32. Thisconfiguration enables the access tip 32 to penetrate the vessel wall atan access site 20. As the device is advanced further, the vessel wallmay reversibly widen due to the increased cross-sectional area of theaccess tip 32. Since the vessel wall is elastic, it will typicallyrecoil upon removal of the access tip 32 from the vessel wall. Thecross-sectional area of access tip 32 may be substantially circular orhave another geometrical cross-sectional shape such as an ellipse.

Referring now to FIG. 7, an alternative configuration of an access tip32 is shown. The access tip 32 is shown associated with the distal end35 of the elongated member 31. Aperture 38 is located at or near thedistal end 35 of the elongated member 31. The aperture 38 can be placedin fluid communication with the proximal end 33 of the elongated member31 by the injection lumen 36.

The access tip 32 can be configured such that the cross-sectional areahas substantially angular features, such as the cross-section shown inFIG. 7A. In this configuration, the access tip 32 includes edges spacedcircumferentially from one another. These edges may further comprisevarying edge sharpness. In further accordance with this configuration,and as illustrated in FIG. 7, the edge can be sharper at a distal sharpedge segment 44 than at a proximal blunt edge segment 46. Accordingly,the tip 32 can access the extravascular space through a coronary vesselwall 22 by creating a relatively small penetration compared to thecross-sectional area of the distended access site 20 once the device isadvanced further.

In a further configuration, the aperture 38 may be positioned along alateral surface of the access tip 32 or elongated member 31. In thiscase, the distal end 35 of the access tip 32 may be made to be moreatraumatic by using a domed construction, for example. A configurationthat is in accordance with this concept will now be explained in greaterdetail.

Referring to FIG. 8, a distal end 35 of an agent delivery device inaccordance with a further configuration is shown. The device includesapertures 38 positioned in the lateral wall of the elongated member 31near its distal end 35. An access tip 32 is shown having a domed distalend 35. A sleeve 47 may be sized and dimensioned to be disposed over theelongated member 31 and/or positioned in a first location, whereby theapertures 38 may be covered, preventing fluid from exiting from theinjection lumen 36 of the device through the apertures 38 into thesurrounding environment.

Referring now to FIG. 9, the device is shown in a second orientationwherein the distal end 35 of the device has accessed the extravascularspace through the vessel wall. During advancement of the device into theextravascular space, the vessel wall has moved the sleeve 47 to a secondlocation that is proximal to the first location. This hereby may uncoverthe apertures 38 and/or may permit the delivery of an agent 49 throughthe injection lumen 36 into the surrounding extravascular space.

In a further configuration, the device may be configured such that asleeve 47 is located distal to the apertures 38 when it is in a firstposition. In this configuration, delivery of an agent from the injectionlumen 36 into the surrounding environment may be possible. The sleeve 47is designed to remain within the first position unless a threshold forceis applied to it. For example, the force applied by the vessel wall tothe sleeve 47 as the device is advanced through the vessel wall into theextravascular space may be lower than the threshold force. By this sameexample, the force applied by the myocardium as the device is advancedthrough the vessel wall into the heart muscle may be greater than thethreshold force. When the threshold force is exceeded, the sleeve 47 maymove to a second location, wherein the sleeve 47 covers the apertures 38and delivery of an agent from the injection lumen 36 into thesurrounding environment is may be limited. Accordingly, a device isprovided that may permit delivery of an agent into the extravascularspace but may inhibit delivery of an agent if the myocardium ismistakenly accessed through the coronary vessel wall 22.

Referring now to FIG. 10, a further configuration of a distal end 35 ofan agent delivery device is shown. An elongated member 31 is provided,and further, an access tip 32 is shown at or near the distal end 35 ofthe elongated member 31, being in association with the elongated member31. A biasing element 48 may be associated with both the elongatedmember 31 and the access tip 32. In accordance with this configuration,the biasing element 48 may be a compression spring that acts between theelongated member 31 and the access tip 32, thereby biasing the accesstip 32 toward a distal first position. If a sufficient compressive loadis placed on the access tip 32, it may cause compression of the biasingelement 48, and may therefore move the access tip 32 toward a secondposition that is proximal relative to the first position.

In further accordance with the presently described configuration, anaperture may be located in the elongated member 31 proximal to theproximal end 33 of the access tip 32 when the access tip 32 is in thefirst position. Further, when the access tip 32 is moved to the secondposition, the aperture may be sealed by the access tip 32, therebyinhibiting delivery of an agent from an injection lumen 36 through theaperture into the surrounding environment.

Accordingly, the access tip 32 may be designed to remain within thefirst position unless a threshold force is applied to it. For example,the force applied by the vessel wall to the access tip 32 as the deviceis advanced through the vessel wall into the extravascular space may belower than the threshold force. By this same example, the force appliedby the myocardium as the device is advanced through the vessel wall intothe heart muscle may be greater than the threshold force. When thethreshold force is exceeded, the access tip 32 may move to the secondposition, wherein aperture 38 may be sealed and delivery of an agentfrom the injection lumen 36 into the extravascular space may beinhibited. Accordingly, a device may be provided that permits deliveryof an agent into the extravascular space, but inhibits the delivery ofan agent if the myocardium is mistakenly accessed through the coronaryvessel wall 22.

A method for delivering a substance into the extravascular space isprovided. The method may include several acts or steps performed invarious orders performed in various orders including the introduction ofa device, as embodied in the examples above, into the vascular system ofa patient. For the purposes of understanding, it should be realized thatthe catheter may be tracked into a coronary vessel, including vesselsthat are arteries or veins. Although the device may be tracked to anypoint at which the extravascular space may be accessed through thevessel wall, it may be desirable to track the device to a distal regionof the coronary vessel. This may ensure that the distal end 35 of thedevice is within a region of the coronary vessel with relatively lowflow velocities and reduces the risk of significant blood loss if thevessel is inadvertently dissected. The access tip 32 of the device maybe advanced until it contacts and/or penetrates the vessel wall. Thismay happen, for example, when the device is tracked through a vesselwith a given curvature.

After penetrating the coronary vessel, the device may be advanced farenough to ensure that an aperture of the device is within theextravascular space. A substance such as a therapeutic agent may then beinjected through an aperture of the device into the extravascular space.The substance may disperse within the extravascular space by the naturalmixing action of the heart 10 and the substance may be administered tothe desired areas through this dispersion.

After delivering the substance, the device may be removed into thecoronary vessel entirely. Secondary acts or steps may be utilized toclose the access site, if blood loss through the access site seemsexcessive. This determination may be made using standard medicalvisualization technologies, such as fluoroscopy. An example of asecondary act is the inflation of an angioplasty balloon within theaccess region to facilitate closure of the access site.

Referring now to FIG. 11, a distal portion of a further configuration ofan agent delivery device is shown. In this configuration, the deviceincludes an elongated member 31 having a proximal end and a distal end35. A flexible tip 52 is disposed adjacent the distal end 35, and may beconstructed in a coiled configuration. The flexible tip 52 may beatraumatic to the vessel wall 22, allowing the elongated member 31 to betracked through a tortuous vessel anatomy. The device further includesan exit port 50 positioned in the elongated member 31 that places aninternal lumen (not shown) disposed within the elongated member 31 influid communication with the surrounding environment. The internal lumenmay be sized and dimensioned to receive an injection member 51. Theinjection member 51 has a proximal end and a distal end 35 and furtherincludes an injection lumen that permits fluid communication between theproximal end and the distal end 35. An aperture (not shown) may bepositioned at or near the distal end 35 of the injection member 51,placing the injection lumen in fluid communication with the surroundingenvironment.

Further, the injection member 51 may be movable within the internallumen of the elongated member 31 and may be positioned in a firstretracted position wherein the distal end 35 of the injection member 51is disposed within the internal lumen of elongated member 31, or it maybe positioned in a second extended position wherein the distal end 35 ofthe injection member 51 is not disposed within the internal lumen ofelongated member 31.

In further accordance with this configuration, the device may include anarcuate member 60 that may be associated with the elongated member 31 ina location adjacent and opposite to the exit port 50. This arcuatemember 60 may bias a portion of the elongated member 31 toward anarcuate configuration.

The arcuate member 60 may comprise a curved metal band, the metal beingdeformable, having a shape-memory, or both, for example. A plasticmaterial may be used to form the arcuate member 60.

In a further configuration, the arcuate configuration of the device canbe achieved by shaping the device body. This can be done, for example,by placing the device body in a curve and subsequently heating andcooling it as necessary to cause the body to reshape in an arcuateconfiguration.

It will be appreciated that when tracking the arcuate member 60 of thedevice through a curved coronary vessel, the arcuate member 60 may urgethe device to self-orient within the curve such that the arcuate member60 may be aligned with the vessel curve. It will be appreciated furtherthat since the arcuate member 60 is located opposite to the exit port 50of the device, the device may self-orient within the vessel curve suchthat the exit port 50 may be near the outer curve of the vessel.Referring again to FIG. 11, accordingly, the exit port 50 of the devicemay face the extravascular space 16 rather than the myocardium 10 whenthe arcuate member 60 is tracked through a curved section of a coronaryvessel. Therefore, when the injection member 51 may be advanced from aretracted position to an extended position. The injection member 51 maypenetrate the coronary vessel into the extravascular space.

Referring now to FIG. 12, a further configuration of a distal end 35 ofa device for localized agent delivery is shown in accordance with thepresent disclosure. The instant configuration includes an elongatedmember 31 and a flexible tip 52. A plurality of exit ports 50 may beincluded within the elongated member 31, each exit port 50 may beadjacent to and/or spaced apart from the other.

The plural exit ports 50 may provide at least one device advantage.First, the reduction in cross-sectional material of elongated member 31may produce a more flexible section, which may be capable of trackingthrough more tortuous anatomy. Also, the exit ports 50 may naturallyalign with the plane of the vessel curvature, potentially resulting in aself-orientation of at least one exit port 50 toward the extravascularspace. Additionally, as the exit port 50 section of the device tracksthrough a vessel bend, the resulting curve in the device may cause thedistal and proximal edges of at least one exit port 50 to separate evenfurther. In combination with the self-orientation of the exit port 50,this may provide a larger port for the injection member 51 to beadvanced through and/or directed along the tangential direction line 19.

Referring now to FIG. 13, a further configuration of a distal end 35 ofa device for localized agent delivery is shown. The device includes anelongated member 31 and a flexible tip 52. Additionally, the elongatedmember 31 includes an exit port 50. An injection member 51 can bereceived within the elongated member 31 and be movable between aretracted and extended position through the exit port 50. A hingeelement 62 may be disposed adjacent to the exit port 50. The hinge maybe a separate element from the elongated member 31. For example, theelongated member 31 may have distal and proximal portions that areconnected by a pin, which serves as a hinge. Alternatively, the hingemay be a living hinge. For instance, a reduced cross-sectional areaportion of the elongated member 31 may have enough flexibility for theelongated member 31 to articulate back and forth, thus acting as ahinge.

Further still, the device may include an actuation member or cord 64having a distal end 35 and a proximal end. The distal end 35 may beassociated with the elongated member at a position distal to the exitport 50. The actuation member or cord 64 may have a low profile and/ormay be constrained relative to the elongated member 31 over at least aportion of the device length.

Referring now to FIG. 14, in further accordance with this disclosure, atensile load is applied to the actuation member or cord 64, therebyapplying a moment arm to the elongated member 31 about the hinge. Thismay cause a strain in the elongated member 31 that may further widen theexit port 50. In addition, the resulting curve in the elongated member31 may promote self-orientation of the exit port 50 toward theextravascular space, as previously described, due to the naturaltendency of curvatures to align with each other. The combination of exitport 50 orientation and exit port 50 widening may permit easieradvancement of the injection member 51, and/or may provide increasedconfidence that the injection member 51 will be directed toward theextravascular space along tangential direction line 19, when advanced.

Referring now to FIGS. 15 and 16, a further configuration is shown. Inthis case, actuation member or cord 64 is constructed from an elasticmaterial and associated with the elongated member 31 in a positiondistal and proximal to the exit port 50. The actuation member mayprovide a natural biasing moment upon the elongated member 31 about thehinge, as a result of its natural tendency to shorten in length.

As shown in FIG. 15, the tendency of the device to curve in the exitport section may initially be resisted by the advancement of aninjection member 51 through the elongated member 31 distal to the exitport 50. The injection member 51 may provide sufficient resistance tothe moment exacted upon the hinge by the actuation member or cord 64 toallow enough device structural rigidity to allow effective trackingthrough the anatomy to the treatment site without buckling. When thetreatment site is reached, the injection member 51 may be retracted to asecond position proximal to the exit port 50. In this second position,there may be reduced resistance to the moment caused by the actuationmember or cord 64, and the device may be bent at the hinge sectionresulting in an overall curve of the device in that area and a tendencyof the distal and proximal edges of the exit port 50 to separatefurther.

Referring now to FIG. 16, a third position of the injection member 51 isshown. The curvature of the device in the exit port section has resultedin self-orientation of the exit port 50 toward the extravascular spaceand has urged the exit port 50 to lengthen as described above.Therefore, advancement of the injection member 51 to the third positionmay ease and the injection member 51 may be directed toward theextravascular space.

A method for delivering a substance into the extravascular space isprovided. The method may include several acts or steps performed invarious orders, including the introduction of a device as embodied inthe examples above, into the vascular system of a patient. For thepurposes of understanding, it should be realized that the catheter mightbe tracked into a coronary vessel, including vessels that are arteriesor veins. Although the device may be tracked to any point at which theextravascular space may be accessed through the vessel wall, it may bedesirable to track the device to a distal region of the coronary vessel.This may ensure that the distal end 35 of the device is within a regionof the coronary vessel with relatively low flow velocities and mayreduce the risk of significant blood loss if the vessel is inadvertentlydissected.

The device may be manipulated until the exit port 50 of the device selfaligns with the outer radius of a vessel curve. The orientation mayresult from the tendency of a curve in the device to align with a curveof the vessel. The curve of the device may be due to a natural bias ofthe device, or the actuation of the device from a less curvaceous to amore curvaceous state, as explained above. Following alignment of theexit port 50, an injection member 51 may be advanced, penetrating thecoronary vessel.

After penetrating the coronary vessel, the injection member 51 may beadvanced far enough to ensure that the distal end 35 of the injectionmember 51 is within the extravascular space. A substance such as atherapeutic agent may then be injected through the injection member 51,into the extravascular space. The substance may disperse within theextravascular space by the natural mixing action of the heart 10 and thesubstance may be administered to the desired areas through thisdispersion.

After delivering the substance, the injection member 51 may be removedinto the coronary vessel entirely, through the vessel access site.Secondary acts or steps may be utilized to close the access site, ifblood loss through the access site seems excessive. An example of asecondary step is the inflation of an angioplasty balloon within theaccess region to facilitate closure of the access site.

Referring now to FIG. 17, a further configuration of a distal end 35 ofa device for local agent delivery is shown. The device includes anelongated member 31 having a distal end 35 and a proximal end andfurther includes a flexible tip 52 disposed adjacent the distal end 35.The flexible tip 52 may improve the trackability of the device throughan anatomy. At least one exit port 50 may be disposed within theelongated member 31 and may place an internal lumen of the elongatedmember 31 in fluid communication with the surrounding environment. Atleast one injection member 51 may be received within the internal lumenof the elongated member 31 and may be movable between a first retractedposition and a second extended position, as shown. The injection member51 may be configured and dimensioned to enable it to penetrate acoronary vessel wall 22 when advanced from the first toward the secondposition.

In one configuration, a plurality of injection members 51 may bedisposed within the elongated member 31. As the plurality of injectionmembers 51 are advanced to a second position, they may penetrate throughthe coronary vessel wall 22 at spaced access sites. At least one ofthese injection members 51 may be directed toward the extravascularspace, permitting delivery of an agent thereto.

Referring now to FIG. 18, a further configuration of a device is shown.The device includes injection members 51 that are configured to extendsubstantially in a transverse direction or plane when they are extendedfrom a first retracted position to a second position.

Accordingly, referring to FIG. 19, the injection member 51 may extend ina curvilinear fashion when viewed from an end of the device. It will beappreciated that the injection members 51 may initially extend in adirection that is substantially perpendicular to the coronary vesselwall 22, thereby facilitating penetration of the vessel wall, and maysubsequently curve along a path that is substantially parallel to thecoronary vessel wall 22. This subsequent direction may reduce thepotential of penetrating the pericardial sac, since the potentialcontact angle between the injection member 51 and the pericardial sac,as well as the penetration depth, may be reduced.

A method for delivering a substance into the extravascular space isprovided. The method may include several acts or steps performed invarious orders, including the introduction of a device as embodied inthe examples above, into the vascular system of a patient. For thepurposes of understanding, it should be realized that the catheter mightbe tracked into a coronary vessel, including vessels that are arteriesor veins. Although the device may be tracked to any point at which theextravascular space may be accessed through the vessel wall, it may bedesirable to track the device to a distal region of the coronary vessel.This may ensure that the distal end 35 of the device is within a regionof the coronary vessel with relatively low flow velocities and mayreduce the risk of significant blood loss if the vessel is inadvertentlydissected.

Once the device is positioned in the desired location, an injectionmember 51 may be advanced through the device exit ports 50, penetratingthe coronary vessel. After penetrating the coronary vessel, an injectionmember 51 may be advanced far enough to ensure that the distal end 35 ofthe injection member 51 is within the extravascular space. A substancesuch as a therapeutic agent is may then be injected through theinjection member 51, into the extravascular space. The substance maydisperse within the extravascular space by the natural mixing action ofthe heart 10 and the substance may be administered to the desired areasthrough this dispersion.

After delivering the substance, the injection member 51 may be removedinto the coronary vessel entirely, through the vessel access site.Secondary acts or steps may be utilized to close the penetration, ifblood loss through the penetration seems excessive. An example of asecondary step is the inflation of an angioplasty balloon within thepenetration region to facilitate closure of the penetration.

Referring now to FIG. 20, a distal end 35 of a further configuration ofa device for local agent delivery is shown. The device includes anelongated member 31 having a distal end 35 and a proximal end. Anexpandable section 70 may be positioned at or near the distal end 35 ofthe elongated member 31 and an injection member 51 may be associatedwith the expandable section 70. The device can further include anexpansion actuation member 76 that can be moved between a first positionand a second position. In the first position, the expandable section 70may reside in a low profile configuration, making it easier for thedevice to be tracked through the anatomy.

Referring now to FIG. 21, by advancing the expansion actuation member 76to a second position, the expandable section 70 may be contacted and/orurged toward an expanded configuration. This expansion may move theinjection member 51 in a direction lateral to the elongated member 31axis. When disposed within a coronary vessel, this can move theinjection member 51 through the coronary vessel wall 22 and/or into theextravascular space.

In each of the preceding two configurations, the device is shown with ablunt distal end 35. It will be appreciated that these configurationsmay include a flexible tip 52 or a guidewire lumen for tracking over aguidewire 71, as previously disclosed and in accordance with the presentdisclosure.

A method for delivering a substance into the extravascular space isprovided in accordance with the present disclosure. The method mayinclude several acts or steps performed in various orders, including theintroduction of a device as embodied in the examples above, into thevascular system of a patient. For the purposes of understanding, itshould be realized that the catheter might be tracked into a coronaryvessel, including vessels that are arteries or veins. Although thedevice may be tracked to any point at which the extravascular space maybe accessed through the vessel wall, it may be desirable to track thedevice to a distal region of the coronary vessel. This may ensure thatthe distal end 35 of the device is within a region of the coronaryvessel with relatively low flow velocities and may reduce the risk ofsignificant blood loss if the vessel is inadvertently dissected.

Once the device is positioned in the desired location, an expandablesection 70 of the device may be actuated, to bring an injection member51 toward the coronary vessel wall. The injection member 51 may beadvanced until it penetrates the coronary vessel.

After penetrating the coronary vessel, an injection member 51 may beadvanced far enough to ensure that the distal end 35 of the injectionmember 51 is within the extravascular space. A substance such as atherapeutic agent may then be injected through the injection member 51,into the extravascular space. The substance may disperse within theextravascular space by the natural mixing action of the heart 10 and thesubstance may be administered to the desired areas through thisdispersion.

After delivering the substance, the injection member 51 may be removedinto the coronary vessel entirely, through the vessel access site. Thismay be facilitated by the retraction of the expandable section 70.Secondary acts or steps may be utilized to close the access site, ifblood loss through the access site seems excessive. An example of asecondary act or step may include the inflation of an angioplastyballoon 72 within the access region to facilitate closure of the accesssite.

Referring now to FIG. 22, a further configuration of the expandablesection 70 is shown. The expandable section 70 may include an injectionmember 51 and a composite member 80 associated with each other at a weldpoint 82. This configuration represents a further construction for theexpandable section 70 that may offer a manufacturability advantage. Theoperation of the expandable section 70 may be controlled by the positionof the expansion actuation member 76, as previously described.

Referring now to FIG. 23, a further configuration of a device forlocalized agent delivery is shown. The device includes a plurality ofinjection members 51, shown here in a deployed configuration advancedthrough the coronary vessel wall 22. At least one injection member 51may be inserted within the myocardium of the heart 10 and at least oneinjection may have accessed the extravascular space.

Further, the proximal end of each injection member 51 may be associatedwith a separate luer, thereby placing a syringe 77 in fluidcommunication with the injection lumen 36 disposed within the respectiveinjection member 51. Therefore, if an agent is delivered through theluer of the injection member 51 disposed within the heart myocardium,then the agent may be delivered to the heart myocardium. Likewise, if anagent is delivered through the luer of the injection member 51 disposedwithin the extravascular space, then the agent may be delivered to theextravascular space.

Accordingly, after advancing the injection members 51 through thecoronary vessel wall 22, contrast agent can be delivered from a syringe77 through the luer to identify under fluoroscopy whether the respectiveinjection member 51 is disposed within the extravascular space. Atherapeutic agent can be delivered from a syringe 77 to theextravascular space, after, for example, the appropriate injectionmember 51 is identified using contrast agent.

In accordance with the present disclosure, an alternative method ofidentifying the injection member 51 location is provided. Afteradvancing the injection members 51 through the coronary vessel wall 22,a vacuum may be applied to the luer. This may be accomplished throughthe use of a syringe 77, for example. If extravascular fluid iswithdrawn into the syringe 77, then the respective injection member 51is likely disposed within the extravascular space. Otherwise, it may bedetermined that the injection member 51 is probably not disposed withinthe extravascular space.

It will be understood that these methods of identifying the position ofthe injection members 51 relative to the extravascular space can applyto any of the configurations described above, in accordance with thepresent disclosure.

Referring now to FIG. 24, a further configuration of a device forlocalized agent delivery is shown. The device includes an elongatedmember 31 having a distal end 35 and a proximal end. An injection lumen36 is disposed therebetween. A luer may be associated with the proximalend 33 of the elongated member 31 and may permit the attachment of asyringe 77 and/or communication of an agent through injection lumen 36.

In this configuration, a detachable tip 90 may be associated with thedistal end 35 of the elongated member 31. The detachable tip 90 mayinclude several elements that may contribute to the structure andfunction of the component. A head 92 may be disposed near the proximalend of the detachable tip 90. The head 92 may be configured anddimensioned to fit within the injection lumen 36 and may include aproximal surface that can be acted upon by a fluid delivered through theinjection lumen 36. The head 92 may have a distal surface that may actto affect the distal movement of the removable tip through tissue.

A shank 94 may be associated with the head 92 and/or with a toothelement 96. The tooth 96 may be disposed at or near the distal end ofthe detachable tip 90. It may include a cross-sectional area that mayreduce in the distal direction. This may permit the distal region of thetooth 96 to penetrate tissue with relative ease. As the tooth 96 isadvanced through tissue, the tissue may be distended around the toothsurface. After the proximal end of the tooth 96 has been insertedthrough tissue, the tissue may recoil toward the profile of the shank94. In this way, an area of tissue may act upon a proximal end of thetooth 96 to resist movement of the detachable tip 90 in a proximaldirection. In cooperation, the elements of the detachable tip 90 maypromote retention of the component within tissue.

Referring now to FIG. 25, in one configuration, the elongated member 31may be advanced through the coronary anatomy until the distal end 35 iswithin a vessel bend. As discussed previously, the vessel bend may urgethe distal end 35 toward the greater curve of the vessel. As theelongated member 31 is advanced further, the distal end of the tooth 96may penetrate the coronary vessel wall 22, entering into theextravascular space. The device can be advanced until the externalsurface of the coronary vessel wall 22 is proximal to the tooth 96.

Detachment of the tip can be accomplished in several ways. In oneconfiguration, the device can be retracted. The retention force placedon the proximal end 33 of the tooth 96 by the coronary vessel wall 22may be greater than the retention force applied to the head 92 by theinjection lumen 36. This may result in the tip detaching within thecoronary vasculature, with the tooth 96 substantially disposed withinthe extravascular space.

Further, a fluid such as saline or contrast agent can be deliveredthrough the injection lumen 36. The fluid pressure may act upon theproximal surface of the head, urging the tip to detach from theelongated member 31.

In another configuration, the detachable tip 90 may be formed from abioabsorbable material. This material could be poly(alpha-hydroxyesters), polylactic acids, polylactides, poly-L-lactide,poly-DL-lactide, poly-L-lactide-co-DL-lactide, polyglycolic acids,polyglycolide, polylactic-co-glycolic acids, polyglycolide-co-lactide,polyglycolide-co-DL-lactide, polyglycolide-co-L-lactide, polyanhydrides,polyanhydride-co-imides, polyesters, polyorthoesters, polycaprolactones,polyanhydrides, polyphosphazenes, polyester amides, polyester urethanes,polycarbonates, polytrimethylene carbonates,polyglycolide-co-trimethylene carbonates, poly(PBA-carbonates),polyfumarates, polypropylene fumarate, poly(p-dioxanone),polyhydroxyalkanoates, polyamino acids, poly-L-tyrosines,poly(beta-hydroxybutyrate), polyhydroxybutyrate-hydroxyvaleric acids,combinations thereof, chitosan, PBT, 4-hydroxybutyrate,3-hydroxybutyrate, or PEG, to name only a few. Further still, atherapeutic agent may be integrally formed within the detachable tip 90structure. Further, a therapeutic agent may be applied to a surface ofthe detachable tip 90 in the form of a coating, for example.Accordingly, after the tip 90 is disposed within the coronaryvasculature, it may begin to degrade, thereby releasing therapeuticagent into the extravascular space.

An advantage of this configuration may include that the access site 20in the coronary vessel wall 22 will likely naturally heal and close asthe detachable tip 90 degrades within the body. This may reduce the needfor subsequent closure techniques after removing the device from theanatomy.

A method for delivering a substance into the extravascular space isprovided. The method may include several acts or steps performed invarious orders, including the introduction of a device as embodied inthe examples above, into the vascular system of a patient. For thepurposes of understanding, it should be realized that the catheter maybe tracked into a coronary vessel, including vessels that are arteriesor veins. Although the device may be tracked to any point at which theextravascular space may be accessed through the vessel wall, it may bedesirable to track the device to a distal region of the coronary vessel.This may ensure that the distal end 35 of the device is within a regionof the coronary vessel with relatively low flow velocities and mayreduce the risk of significant blood loss if the vessel is inadvertentlydissected.

The device may be advanced until the detachable tip 90 has penetratedthe coronary vessel. This may be facilitated by tracking the devicethrough a coronary vessel with a given curvature.

After penetrating the coronary vessel, the tip 90 may become detached,remaining in communication with the extravascular space. The detachabletip 90 may degrade, releasing a substance that may disperse within theextravascular space by the natural mixing action of the heart 10 and thesubstance may be administered to the desired areas through thisdispersion. After delivering the detachable tip 90, the device body maybe removed from the coronary vessel.

Referring now to FIG. 26, an alternative configuration of a device forlocalized agent delivery is shown having a fluid injection feature. Thefluid injection lumen 108 has a proximal end 33 and a distal end 35,with an injection port 109 that may be disposed adjacent the distal end35. The device includes an elongated member 31 having a proximal end 33and a distal end 35. A luer fitting 34 may be associated with theproximal end 33. The luer fitting 34 may include at least two separateluer channels (not shown). At least one luer channel may be incommunication with the fluid injection lumen 108. At least one luerchannel is in communication with an inflation lumen (not shown) definedbetween the elongated member 31 and a guidewire lumen 112 disposedwithin the elongated member 31. The guidewire lumen 112 may beconfigured and dimensioned to receive a guidewire 71 thereby permittingthe device to be tracked over a guidewire 71 disposed within a vascularanatomy. The device may include an expandable structure 110 that may bedisposed at or near the distal end 35 of the device and/or may be placedin fluid communication with the inflation lumen. The expandablestructure 110 may include a single balloon element or multiple balloonelements. The injection port 109 may be further disposed adjacent thesurface of the balloon structure.

Referring now to FIG. 27, the expandable structure 110 may be formedfrom two or more separate balloon elements, although it may also beformed from a single balloon element. In this configuration, eachballoon element may be formed in a substantial “D” shape during theballoon forming process, although other configurations are possible. Forinstance, two balloons with circular cross-sections can be constrainedby a tubular sheath, urging them toward a substantially “D” shapedconfiguration. The balloon elements can be positioned on opposite sidesof the fluid injection lumen 108 and the guidewire lumen 112 in order tomaintain a balanced profile and to ease deliverability of the devicethrough the coronary anatomy.

The expandable structure 110 may be formed from an expandable metallicor plastic structure, such as a self-expanding nitinol scaffold. Thistype of structure would permit maintained blood flow within the vesseleven during expansion. It may be desirable to include a sheath componentaround the expandable structure 110 in order to separate the vessel wallfrom the blood flow, potentially providing an advantage that will beexplained in greater detail below.

Referring now to FIG. 28, a further configuration of the device having afluid injection feature is shown. In this configuration, the device doesnot include a fluid injection lumen 108. Fluid may be delivered throughthe inflation lumen into the balloon element. Fluid may ejected throughthe fluid injection port 109 formed in the surface of the balloonelement.

A method is provided for delivering an agent into the extravascularspace using a device with an injection port 109. A guidewire 71 may betracked through the coronary anatomy, such as to a distal vessellocation. The device may be tracked over the guidewire 71 until theballoon structure is adjacent the desired treatment location. A fluidsource may be attached to the luer fitting 34 (FIG. 30) and pressurizedfluid may be delivered through the inflation lumen of the device,causing the balloon structure to expand against the coronary vessel wall22. This may bring the injection port 109 into close proximity with thecoronary vessel wall 22. An agent source such as a syringe 77 may beattached to the luer fitting 34, and agent may be delivered underpressure through the injection port 109. As described previously, thiscan be accomplished with or without the use of a fluid injection lumen108, depending upon the configuration of the device. The agent may bedelivered at a sufficient velocity to eject through the injection port109 and/or to penetrate through the coronary vessel wall 22 into theextravascular space.

With this configuration, the fluid jet could permit the coronary vesselto recoil to a substantially closed position after agent injection.Additionally, the expandable structure 110 can remain expanded afterfluid injection, permitting a chance for the vessel to heal adequatelybefore re-establishing blood flow within the coronary vessel. As aresult, this configuration may reduce the potential of excessivebleeding into the extravascular space.

Referring now to FIG. 29, a further configuration of a device for localagent delivery is provided. The device includes a stent structure 120with at least one strut element 122. A series of strut elements 122 canbe arranged in circumferentially expandable rings. The stent structure120 includes at least one protrusion 124 associated with a stent strutand which extends from the stent strut. As shown, the at least oneprotrusion 124 is formed in a direction that is substantially parallelto the direction of stent expansion. It will be understood, however,that the protrusion 124 can extend from the stent strut at any angularorientation relative to the stent strut in accordance with thisdisclosure. The angular orientation may be such that it may allow theprotrusion to engage with the tissue.

Referring now to FIG. 30 and FIG. 31, a further configuration is shown.The protrusions 124 are formed in a direction that is substantiallytangential to the stent circumference. This may allow the protrusions toembed within the coronary vessel wall 22 to a shallower depth whilemaintaining the same volume to surface area ratio for the protrusions124.

The stent structure 120 of this configuration can be formed from a metalsuch as stainless steel, cobalt-chromium, MP35N, or Nitinol. It may alsobe formed from a plastic such as nylon, or a bioabsorbable material suchas poly-L-lactide, polyester amide, iron-silicon composite, or any othermetallic or polymeric bioabsorbable material. A number of othermaterials and methods for fabricating the stent may be used.

In accordance with this disclosure, a therapeutic agent may beintegrally formed within the protrusions 124. In another example, atherapeutic agent may be subsequently added as a surface coating, forexample.

After deploying the stent by, for example, releasing a self-expandingstent to allow it to expand or inflating a balloon to expand a balloonexpandable stent, the protrusions 124 may penetrate the coronary vesselwall 22. Therapeutic agent may subsequently be released into theextravascular space. This release may occur as a result of degradationof protrusions 124 in the case of bioabsorbable protrusions, or due tothe surface release of therapeutic agent in the case of surface coatedprotrusions, or for other reasons.

This configuration may eliminate the need to close the access sitewithin the coronary vessel, since the stent structure 120 itself mayseal off the penetration, thereby preventing excessive bleeding into theextravascular space.

In accordance with each of the configurations disclosed above, it may bedesirable to promote healing of a access site in the coronary vesselwall 22 after and/or during removal of the device into the coronaryvessel. A method of promoting healing of a vessel access site can beprovided that includes application of a vasoconstrictor through a devicelumen adjacent to the access site. The vasoconstrictor may be alcohol,for example, or any other agent suitable for urging the vessel to closethe access site.

Pressure can be applied to the access site after removing the deviceinto the coronary vessel. This can be accomplished in a number of ways.In one example, a balloon may be inflated within the coronary vesseladjacent to the access site. The balloon surface may contact the vesselpenetrate, providing pressure to the vessel area and/or promotingclosure of the access site.

In an alternative configuration, an expandable structure 110 such as aNitinol stent may include a sheath disposed about an external surface ofthe stent. The expandable structure 110 may thus be deployed adjacent tothe vessel access site, thereby contacting the vessel access site andapplying pressure to the vessel area and/or promoting closure of theaccess site.

In many of these configurations, the device is used to deliver an agent,such as a therapeutic agent, into the extravascular space in order totreat vascular diseases. It should be appreciated that the devices mayserve alternative purposes. For example, the devices could be used todeliver substances into the myocardium of the heart 10. This can bebeneficial, for example, in the delivery of cells to ischemic hearttissue, fostering cell therapy of the damaged tissue. Also, devices inaccordance with the embodiments described above could be used to deliveragents into other patient tissues or spaces that surround bodily lumens.For example, such devices may be used to penetrate through a urethra inorder to deliver an agent into a prostate gland. Further, such devicescould access the liver through the walls of a hepatic vein. Theseexamples are intended to show the breadth of applications that there arefor a device in accordance with this disclosure. It will therefore beappreciated that the embodiments disclosed above are not intended tolimit the disclosure to any one application, but should instead beregarded as illustrative of the disclosure and its advantages.

It will be further understood that the present disclosure encompassesmany configurations. These configurations may be useful alone or incombination. The above disclosure is intended to be illustrative and notexhaustive. This description will suggest many variations andalternatives to one of ordinary skill in this art. All of thesealternatives and variations are intended to be included within the scopeof the attached claims. Those familiar with the art may recognize otherequivalents to the specific configurations described herein whichequivalents are also intended to be encompassed by the claims attachedhereto.

While the present disclosure is described herein in terms of certainconfigurations or embodiments, various modifications and improvementsmay be made to the disclosure without departing from the scope thereof.Moreover, although individual features of one configuration orembodiment of the disclosure may be discussed herein or shown in thedrawings of the one configuration or embodiment and not in otherconfigurations or embodiments, it should be apparent that individualfeatures of one configuration or embodiment may be combined with one ormore features of another configuration or embodiment or features from aplurality of configurations or embodiments of the disclosure.

The present disclosure, therefore, may be embodied in other specificforms without departing from its spirit or essential characteristics.The described configurations are to be considered in all respects onlyas illustrative and not restrictive. The scope of the invention is,therefore, indicated by the appended claims rather than by the foregoingdescription. All changes which come within the meaning and range ofequivalency of the claims are to be embraced within their scope.

1. A device for localized agent delivery through the wall of a coronaryvessel, comprising: an elongated member having a first end and a secondend and a longitudinal axis therebetween; a tip adjacent the second end,the tip having a distal end and a proximal end, wherein the distal endis narrower than the proximal end; and a lumen disposed within theelongated member and between the first end of the elongated member andthe distal end of the tip, whereby the first end of the elongated memberand the distal end of the tip are in fluid communication.
 2. The deviceof claim 1, wherein the tip has a circular cross-sectional profile. 3.The device of claim 1, wherein the tip has a non-circularcross-sectional profile.
 4. The device of claim 1, further comprising anaperture disposed adjacent the distal end of the tip, the aperture beingin fluid communication with the lumen.
 5. The device of claim 1, furthercomprising: an aperture in the elongated member adjacent the second end,the aperture being in fluid communication with the lumen; and a sleevesized and dimensioned to mate with the elongated member and beingmoveable between a first and second position, whereby in the firstposition the sleeve seals the aperture and in the second position thesleeve does not seal the aperture.
 6. The device of claim 1, furthercomprising a biasing member disposed between the second end of theelongated member and the distal end of the tip, whereby the biasingmember resists motion of the tip between a first tip position and asecond tip position.
 7. A device for localized agent delivery throughthe wall of a coronary vessel, comprising: an elongated member having afirst end and a second end, wherein the elongated member is moreflexible near the second end than near the first end; a longitudinalaxis defined between the first and second end; at least one lumensubstantially aligned with the longitudinal axis between the first endof the elongated member and an exit port adjacent the second end of theelongated member; and at least one injection member disposed within theat least one lumen having a proximal end and a distal end, the distalend being movable from a first position within the at least one lumen toa second position through the exit port, the injection member furthercomprising an injection lumen placing the proximal and distal end influid communication.
 8. The device of claim 7, further comprising asubstantially arcuate member disposed along the elongated member nearthe exit port, whereby the elongated member is biased toward a curvedconfiguration.
 9. The device of claim 8, further comprising a secondexit port disposed opposite the first exit port, whereby the flexibilityof the elongated member near the exit ports is increased and at leastone of the exit ports is biased toward the outer curve when the deviceis placed in a bend.
 10. The device of claim 8, further comprising anactuation cord radially constrained along the elongated member, beingsubstantially misaligned with the exit port and having a proximal endand a distal end, the distal end associated with the elongated memberdistal to the exit port, whereby when a tensile load is placed on theactuation cord the elongated member is biased toward a curvedconfiguration.
 11. The device of claim 7, wherein there are threeinjection members spaced apart in the radial direction and there arethree lumens.
 12. The device of claim 7, wherein the injection memberfollows a substantially radial path between the exit port of theelongated member and the distal end of the injection lumen when in thesecond position.
 13. The device of claim 7, wherein the injection memberfollows a substantially curvilinear path between the exit port of theelongated member and the distal end of the injection member when in thesecond position.
 14. A device for localized agent delivery through thewall of a coronary vessel, comprising: an elongated member having afirst end and a second end and a longitudinal axis therebetween; and adetachable tip dimensioned and configured to be associated with theelongated member.
 15. The device of claim 14, wherein the detachable tipis formed from a bioabsorbable material.
 16. The device of claim 14,wherein the detachable tip further comprises a therapeutic agent.
 17. Adevice for localized agent delivery through a coronary vessel wall, thedevice comprising: an elongated flexible member having a proximal end, adistal end, and a lumen extending therebetween, the proximal end and thedistal end being in fluid communication with each other; an inner memberdisposed within the elongated flexible member and having a proximal endand a distal end, the distal end terminating distal to the distal end ofthe elongated flexible member; an expandable member having a proximalend and a distal end, the expandable member being positioned adjacentthe distal end of the device, the proximal end of expandable memberbeing associated with the elongated flexible member adjacent to thedistal end of the elongated flexible member, and the distal end of theexpandable member being associated with the inner member adjacent to thedistal end of the inner member; and an injection lumen having a firstend adjacent to the proximal end of the elongated flexible member and asecond end adjacent to a surface of the expandable member.
 18. Anendoprosthesis for delivery in a body lumen, the endoprosthesiscomprising: at least one strut element having a strut width and a strutthickness, the strut thickness being defined by a first side opposite asecond side; and at least one protrusion including a therapeutic agent,extending from the strut element so as to access a extravascular spacethrough a coronary vessel wall when the endoprosthesis is delivered. 19.The endoprosthesis of claim 18, wherein the at least one protrusion hasan apex.
 20. The endoprosthesis of claim 18, wherein the at least oneprotrusion extends along a curvilinear path.